Submissions for variant NM_000455.5(STK11):c.465-10C>G

gnomAD frequency: 0.00001  dbSNP: rs1060503780

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000459363	SCV000554122	likely benign	Peutz-Jeghers syndrome	2023-12-04	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001181771	SCV001346978	uncertain significance	Hereditary cancer-predisposing syndrome	2021-10-27	criteria provided, single submitter	clinical testing	This variant causes a C to G nucleotide substitution at the -10 position of intron 3 of the STK11 gene. Splice site prediction tools are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, RNA functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Genome-Nilou Lab	RCV000459363	SCV002057250	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492063	SCV004239726	uncertain significance	Breast and/or ovarian cancer	2023-05-01	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357591	SCV001553103	uncertain significance	Malignant tumor of breast		no assertion criteria provided	clinical testing	The STK11 c.465-10C>G variant was not identified in the literature nor was it identified in the dbSNP, Cosmic, LOVD 3.0, Zhejiang University, or Insight Hereditary Tumors databases. The variant was identified in ClinVar (classified as likely benign by Invitae). The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.